Orelabrutinib
(Synonyms: 奥布替尼,ICP-022) 目录号 : GC39634
Orelabrutinib (ICP-022) is a potent, orally active and irreversible inhibitor of Bruton's tyrosine kinase (BTK). Orelabrutinib has potential antineoplastic activity.
Cas No.:1655504-04-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Orelabrutinib (ICP-022) is a potent, orally active and irreversible inhibitor of Bruton's tyrosine kinase (BTK). Orelabrutinib has potential antineoplastic activity.
Orelabrutinib potently inhibits BTK enzymatic activity with an IC50 value of 1.6 nM. In KINOMEscan assay conducted in parallel at 1 μM against a panel of 456 kinases, orelabrutinib only targets BTK with > 90% inhibition while ibrutinib inhibits additional many other kinases including EGFR, TEC and BMX, demonstrating orelabrutinib's superior kinase selectivity.[2]
Orelabrutinib has a favorable PK profile with an ideal T1/2 (~1.5-4 h) and good oral bioavailability (~20-80%) as well as prolonged BTK target occupancy in preclinical PK/PD studies. The superior selectivity translates into improved safety profile and large safety window in the GLP toxicology studies in rats and dogs.[2]
[1] Wei Xu, et al. Blood (2019) 134 (Supplement_1): 4319. [2] Bin Zhang, et al. Cancer Res 2020;80(16 Suppl):Abstract nr CT132.
| Cas No. | 1655504-04-3 | SDF | |
| 别名 | 奥布替尼,ICP-022 | ||
| Canonical SMILES | O=C(C1=CC=C(C2CCN(C(C=C)=O)CC2)N=C1C3=CC=C(OC4=CC=CC=C4)C=C3)N | ||
| 分子式 | C26H25N3O3 | 分子量 | 427.5 |
| 溶解度 | DMSO: 250 mg/mL (584.80 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3392 mL | 11.6959 mL | 23.3918 mL |
| 5 mM | 0.4678 mL | 2.3392 mL | 4.6784 mL |
| 10 mM | 0.2339 mL | 1.1696 mL | 2.3392 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Orelabrutinib: First Approval
Drugs 2021 Mar;81(4):503-507.PMID:33704654DOI:10.1007/s40265-021-01482-5.
Dysregulation of Bruton's tyrosine kinase (BTK) signalling has been linked to various B cell malignancies and autoimmune diseases. Orelabrutinib (®) is an orally administered, potent, irreversible and highly selective BTK-inhibitor being developed by InnoCare Pharma for the treatment of B cell malignancies and autoimmune diseases. In December 2020, Orelabrutinib received its first approval in China for the treatment of patients with mantle cell lymphoma (MCL) or chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL), who have received at least one treatment in the past. Clinical development of Orelabrutinib for various indications is underway in the USA and China. This article summarizes the milestones in the development of Orelabrutinib leading to this first approval.
Evaluating Orelabrutinib as a novel treatment option for relapsed/refractory chronic lymphocytic leukemia in China
Expert Opin Pharmacother 2022 Dec;23(18):1979-1986.PMID:36329558DOI:10.1080/14656566.2022.2144218.
Introduction: The covalent Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has been approved in the USA for B cell malignancies for almost ten years and has improved the survival of patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Orelabrutinib is a novel, highly selective covalent BTK inhibitor with proven efficacy and acceptable safety profile. In 2020, it was approved for the treatment of relapsed/refractory (R/R) CLL/SLL in China. Areas covered: In this review, we summarized the current clinical trials exploring Orelabrutinib monotherapy or orelabrutinib-based combination regimens in CLL/SLL, especially R/R CLL/SLL. Pharmacodynamics, pharmacokinetics, clinical efficacy and safety of Orelabrutinib are also discussed. Expert opinion: Orelabrutinib selectively inhibits BTK via covalent binding and exhibits linear pharmacokinetics. BTK is the only kinase targeted by Orelabrutinib, and a few off-target toxicities of Orelabrutinib have been reported. The phase I/II trial demonstrated the efficacy and safety of Orelabrutinib in patients with R/R CLL/SLL; however, further clinical trials are needed to compare Orelabrutinib with ibrutinib in patients with R/R CLL/SLL and to evaluate its efficacy and safety in patients with treatment-naive CLL/SLL.
Addition of BTK inhibitor Orelabrutinib to rituximab improved anti-tumor effects in B cell lymphoma
Mol Ther Oncolytics 2021 Apr 3;21:158-170.PMID:33981831DOI:10.1016/j.omto.2021.03.015.
Bruton tyrosine kinase (BTK) inhibitor ibrutinib has been validated as an effective drug to treat B cell malignancies. Combined therapies comprising ibrutinib and anti-CD20 antibodies like rituximab were designed as a backbone in many clinical trials. However, the off-target inhibition of ibrutinib on interleukin-2 (IL-2)-inducible T cell kinase (ITK) may reduce rituximab's antibody-dependent cellular cytotoxicity (ADCC) efficacy. Orelabrutinib (Orel), a novel BTK inhibitor, was designed with high selectivity to BTK. In our study, we demonstrated in preclinical models that Orelabrutinib in combination with rituximab could preserve NK-cell-mediated ADCC induced by rituximab and enhanced the apoptosis of tumor cells in vitro. The addition of Orelabrutinib to rituximab had produced promising combined anti-tumor effects in B cell lymphomas in vivo. Collectively, combination therapy of Orelabrutinib with rituximab would benefit patients with B cell lymphoma, especially those with relapsed or refractory disease.
Bruton Tyrosine Kinase Inhibitors in B-Cell Malignancies: Their Use and Differential Features
Target Oncol 2022 Jan;17(1):69-84.PMID:34905129DOI:10.1007/s11523-021-00857-8.
Starting with the first-in-class agent ibrutinib, the development of Bruton tyrosine kinase (BTK) inhibitors has led to dramatic improvements in the management of B-cell malignancies. Subsequently, more-highly selective second-generation BTK inhibitors (including acalabrutinib, zanubrutinib, tirabrutinib and Orelabrutinib) have been developed, primarily with an aim to reduce off-target toxicities. More recently, third-generation agents including the non-covalent BTK inhibitors pirtobrutinib and nemtabrutinib have entered later-stage clinical development. BTK inhibitors have shown strong activity in a range of B-cell malignancies, including chronic lymphocytic leukaemia/small lymphocytic lymphoma, mantle cell lymphoma, Waldenström's macroglobulinaemia and marginal zone lymphoma. The agents have acceptable tolerability, with adverse events generally being manageable with dosage modification. This review article summarises the evidence supporting the role of BTK inhibitors in the management of B-cell malignancies, including highlighting some differential features between agents.
Orelabrutinib-bruton tyrosine kinase inhibitor-based regimens in the treatment of central nervous system lymphoma: a retrospective study
Invest New Drugs 2022 Jun;40(3):650-659.PMID:35137332DOI:10.1007/s10637-022-01219-5.
Background: Central nervous system lymphoma (CNSL) is an aggressive lymphoma. Orelabrutinib, an oral Bruton tyrosine kinase inhibitor, is a new treatment strategy for CNSL. This study aims to evaluate the efficacy and safety of orelabrutinib-based regimens in the treatment of patients with CNSL. Methods: Twenty-three patients with CNSL were included in this retrospective study. All patients received the orelabrutinib-based regimen. Efficacy was evaluated based on investigators' assessment of overall response rate (ORR), complete response/unconfirmed complete response (CR/CRu), partial response (PR), stable disease (SD), progressive disease (PD), duration of response (DOR), progression-free survival (PFS) and overall survival (OS). The safety of orelabrutinib-based regimens has also been evaluated. Results: A total of 17.39% of patients received orelabrutinib-based regimens for consolidation therapy, and 82.61% of patients for induction therapy (4 newly diagnosed CNSL, 15 relapsed/refractory CNSL). In the newly diagnosed CNSL group, the ORR was 100% (1 CR, 1 CRu, 2 PR). The 6-month DOR rate, 6-month PFS rate, and 6-month OS rate were 100%, 100%, and 100%, respectively. Of the 15 relapsed/refractory CNSL patients, five therapy regimens were applied (Orelabrutinib, n = 3; Orelabrutinib/immunotherapy, n = 3; Orelabrutinib/chemotherapy, n = 2; Orelabrutinib/immunochemotherapy, n = 6; Orelabrutinib/radiotherapy, n = 1). The ORR was 60.00% (4 CR, 5 PR). The 6-month DOR rate, 6-month PFS rate, and 6-month OS rate were 92.30%, 67.70%, and 70.00%, respectively. Twenty-one patients reported adverse events (AEs), and 6 patients experienced grade ≥ 3 AEs. Conclusion: Orelabrutinib-based regimens were efficacious and well-tolerated in patients with CNSL. These combined therapies offer a new potential therapeutic strategy for patients with CNSL.